1. The Field of the Invention
The present invention is related to methods and compositions for use in delivering a pharmacological agent to a patient. More particularly, the present invention is directed to methods and compositions for noninvasive administration of pharmacological agents having sedative, analgesic, or anesthetic properties. 2. The Prior Art
In recent years, a host of potent new drugs have become available for clinical use, and current expectations are that additional potent drugs will continue to become available in the future. In addition to treating specific diseases and conditions, physicians can prescribe drugs that will permit the physician to regulate many body functions and processes. Yet, despite the tremendous advances in the field of pharmacology, physicians continue to administer these new drugs using substantially the same techniques that have been employed for many decades.
Thus, almost all pharmacological agents continue to be administered via two routes, by mouth or by injection, despite the fact that both of these routes suffer from significant disadvantages in particular situations.
The simplest and most prevalent administration route is by mouth. To use this method, a pharmacological agent is incorporated into a tablet, a capsule, or into a liquid base. The patient then ingests an appropriate dose. Oral administration of a drug is extremely convenient, and for many drugs, it will continue to be the method of choice. Such administration is nonthreatening and is painless to the patient. For most patients, it is also very simple.
Nevertheless, oral administration of a drug suffers from the disadvantage that pediatric and geriatric patients frequently have difficulty swallowing pills, and such patients often refuse to cooperate in swallowing a liquid medication. Even more importantly, absorption of a drug into the bloodstream after swallowing a tablet varies from patient to patient. The absorption of the drug is dependent upon the movement from the stomach to the small and large intestines and the effects of secretions from these organs.
Moreover, there is often a substantial delay between the time of oral administration of a drug until it begins to have the desired therapeutic effect on the patient's system. Generally, a drug must pass from the stomach into the small and large intestines before it will be absorbed into the patient's bloodstream; unfortunately, this typically takes forty-five minutes or longer. For some applications, such a delay is unacceptable.
Further, many drugs taken orally are metabolized almost immediately--they are removed from or rendered ineffective by the patient's system before they can have any therapeutic effect. This occurs because the veins from the small and large intestines drain into the liver. Thus, drugs entering the patient's bloodstream through the intestines immediately pass through the patient's liver before distribution throughout the remainder of the patient's body. Unfortunately, upwards of sixty percent of a drug (and essentially one hundred percent of certain drugs) may be removed from the patient's bloodstream during this first pass through the liver; the result is that the oral route of administration is impractical for many drugs.
Yet a further difficulty encountered when administering drugs orally is that dosages are prepared or determined for use with an "average" patient. This is entirely acceptable for many drugs, but some drugs, such as those that have an effect on the patient's central nervous system, have a widely varying effect on different patients, depending upon individual variations in susceptibility to the particular drug utilized.
Underdosing a patient because of a low susceptibility to the drug fails to evoke the response sought by the physician. Overdosing the patient can result in dangerous depression of vital body functions. Moreover, the slow and uncertain response time for the onset of an observable reaction to a drug when taken orally makes it even more difficult to determine a proper dose for a particular patient; the physician may not learn for an hour whether the patient was underdosed or overdosed.
In order to avoid these serious disadvantages inherent in the oral administration route, physicians frequently resort to the injection route for administering many drugs. Injecting a drug (generally intravenously or intramuscularly) results in rapid entry of the drug into the patient's bloodstream; in addition, this type of delivery avoids the removal of large quantities of the drug by the patient's liver that accompanies oral administration. Rather, the drug becomes rapidly distributed to various portions of the patient's body before exposure to the liver; thus, the drug is removed by the liver at a substantially slower rate.
Unfortunately, most patients have at least some aversion to receiving injections. In some patients, this aversion may be so pronounced as to make the use of injections of serious concern to the physician. Since intense psychological stress can exacerbate a patient's debilitated condition, it sometimes becomes undesirable to use injections where the patient is seriously ill or suffers from a debilitating condition or injury.
To compound the problem facing a physician, the individual variation in susceptibility and metabolism with respect to various drugs, which makes it difficult to select an appropriate dose for oral administration is even more profound when utilizing the injection route. This is because smaller doses have an increased effect due to the rapidity in which the drug enters the bloodstream and because large portions of the drug are not immediately metabolized by the liver.
In order to prevent overdosing a patient with potent drugs, a prudent physician typically injects a patient with a lower than average dose, and later supplements the dose with additional injections as they appear necessary. This, of course, makes necessary the use of repeated injections, which in turn greatly increases the stress on the patient. It is not uncommon for a patient to come to fear that it is time for yet another injection every time the patient sees a member of the hospital staff, which is often the case for those most in need of potent drugs.
Considering these problems in medicament administration in light of a specific situation, one of the most difficult tasks facing a physician is preparing a patient psychologically for the rigors of a significant surgical operation and helping the patient through the painful period following surgery. Prior to an operation, it is frequently desirable to administer a drug having a sedative effect. Immediately prior to the operation, it is necessary to anesthetize the patient, and following the operation, it is necessary to administer an analgesic drug.
One common approach to preparing a patient for surgery is to administer a sedative orally. At this stage, quick onset of sedation is not critical; the drug can generally be administered well before its effect is required. Once the patient has been sedated, he is less fearful of injections. Following surgery, the level of pain is often so high that a patient may welcome injections of a fast-acting analgesic.
This is the approach which today is most widely practiced. It is generally successful in assisting a patient through the stress and discomfort of a surgical operation. Nevertheless, it also suffers from some serious disadvantages.
For example, a frightened child will often refuse to ingest a sedative; moreover, the inability to tolerate a potent drug may result in emesis shortly after taking a drug by oral administration. In either case, the child's level of stress will be significantly increased, and it will become even more difficult to elicit the child's cooperation with the physician and hospital staff. Subsequent resort to injections serves to reinforce the child's fears and increases the child's unwillingness to cooperate. It is not uncommon to find an adult patient who has had a traumatic experience of this type as a child, thereby resulting in severe anxieties or fears when facing surgery as an adult.
Another problem commonly arises during the post-surgical treatment of a patient with an analgesic. Pain is an extremely individual experience. Two persons undergoing the same surgical operation may have widely different subjective experiences of pain. Considering the individual experiences of pain as well as the individual variations in the susceptibility to the effects of an analgesic, it is very difficult for a physician to prescribe a suitable dose of analgesic for any particular patient. Again, the typical solution may be to prescribe an "average" dose, which may be too strong or too weak in any particular case. In an attempt to solve this problem, many physicians prescribe pain medication "on demand"; the patient is given pain medication substantially whenever he or she requests it.
As a patient begins to recover, his or her subjective experience of pain will eventually decrease to a point where it is no longer severe. If the patient is receiving pain medication by injection, a patient that has an aversion to injections will eventually reach the point where the act of administering the analgesic becomes stressful. Such a patient may choose to bear much unneeded pain rather than submit to additional injections. Refusing treatment with pain medication can actually reduce a patient's rate of recovery, as well as making the period of recovery more unpleasant for the patient and the hospital staff.
In view of the foregoing, it will be appreciated that it would be an important advancement in the art of administering drugs if suitable methods and compositions could be provided that were capable of rapid action and avoided the disadvantage of immediate metabolism through the patient's liver, yet did not involve injection.
It would also be an important advancement if methods and compositions could be provided that would give a physician control over the administration of medication so that a desired effect is obtained and maintained. It would be of further significant importance if methods and compositions could be provided that would permit a patient to easily control the amount of pain medication he or she receives according to his or her own subjective need for medication. Such methods and compositions are disclosed and claimed herein.